炔丙基甘氨酸增加高肺血流大鼠肺动脉结缔组织生长因子的表达  

Propargylglycine up-regulated connective tissue growth factor expression in rat pulmonary artery with high pulmonary blood flow

作　　者：李晓惠[1] 杜军保[1] 卜定芳[2] 金红芳[1] 唐朝枢[3] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院中心实验室,北京100034 [3]北京大学第一医院心血管病研究所,北京100034

出　　处：《基础医学与临床》2008年第7期681-685,共5页Basic and Clinical Medicine

基　　金：国家杰出青年科学基金(30425010);北京市自然科学基金(7052043);国家重点基础研究发展规划(2006CB503807)

摘　　要：目的探讨硫化氢(H2S)生成酶抑制剂炔丙基甘氨酸(PPG)对高肺血流大鼠肺动脉结缔组织生长因子(CTGF)表达的影响。方法将32只雄性SD大鼠随机分为分流组、分流+炔丙基甘氨酸(PPG)组、假手术组和假手术+PPG组,每组8只。在大鼠高肺血流动物模型上,观察肺组织H2S含量、血浆ET-1含量、肺组织ET-1 mRNA的表达和肺动脉CTGF蛋白表达的变化。结果分流4周后,肺组织H2S含量、血浆ET-1含量、肺组织ET-1 mRNA表达及肺动脉CTGF表达均明显升高(P<0.01);应用PPG干预后,分流+PPG组大鼠H2S含量明显降低;血浆ET-1含量、肺组织ET-1 mRNA的表达及肺动脉CTGF蛋白表达比分流组明显增加(P<0.05)。结论内源性H2S可能通过降低血管活性肽ET-1及CTGF在肺组织的表达参与对高肺血流时肺循环结构与功能的调节。Objective To explore possible impact of endogenous hydrogen sulfide （H2S） on connective tissue growth factor （CTGF） expression in rat pulmonary artery with high pulmonary blood flow. Methods Thirty-two male SD rats, weighing 120 - 140 g, were randomly divided into 4 groups：shunt group, shunt ＋ PPG group, sham group and sham ＋ PPG group. After 4 weeks of experiment, Rat lung tissue HzS content was determined by a modified sulfide electrode method. Plasma ET-1 concentration was detected by radioimmunoactivity, and lung tissue ET-1 mRNA expression of rat was determined by quantitative competitive reverse transcriptional polymerase chain reaction （RT-PCR）. Pulmonary artery connective tissue growth factor （CTGF） protein expression of rats was investigated by immunohistochemistry. Results After 4 weeks of experiment, lung tissue H2S content plasma ET-1, lung tissue ET-1 mRNA and CTGF expression increased significantly in rats of shunt group as compared with that of sham group （P 〈 0. 05）. After administration of PPG for 4 weeks, lung tissue H2S content decreased significantly （ P 〈 0. 0 5 ） . In contrast to rats in shunt group , shunt ＋ PPG group plasma ET - 1 content and lung tissue ET - 1 mRNA expression significantly increased respectively （P 〈 0. 05 ）. Compared with rats of shunt group, shunt ＋ PPG group pulmonary artery CTGF protein expression up-regulated significantly （P 〈 0. 05 ）. Conclusion Endogenous H2 S might be involved in the regulation of pulmonary vascular function and structure in high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expression in lung tissue of rats.

关 键 词：硫化氢 高肺血流 大鼠 内皮素 结缔组织生长因子 

分 类 号：R363[医药卫生—病理学]